Characteristics of maturity onset diabetes of the young in a large diabetes center
Hattersley, Andrew T.
This is the peer reviewed version of the following article: Chambers, C., Fouts, A., Dong, F., Colclough, K., Wang, Z., Batish, S. D., Jaremko, M., Ellard, S., Hattersley, A. T., Klingensmith, G. and Steck, A. K. (2015), Characteristics of maturity onset diabetes of the young in a large diabetes center. Pediatric Diabetes. doi: 10.1111/pedi.12289, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/pedi.12289/abstract .This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Maturity onset diabetes of the young (MODY) is a monogenic form of diabetes caused by a mutation in a single gene, often not requiring insulin. The aim of this study was to estimate the frequency and clinical characteristics of MODY at the Barbara Davis Center. A total of 97 subjects with diabetes onset before age 25, a random C-peptide ≥0.1 ng/mL, and negative for all diabetes autoantibodies (GADA, IA-2, ZnT8, and IAA) were enrolled, after excluding 21 subjects with secondary diabetes or refusal to participate. Genetic testing for MODY 1-5 was performed through Athena Diagnostics, and all variants of unknown significance were further analyzed at Exeter, UK. A total of 22 subjects [20 (21%) when excluding two siblings] were found to have a mutation in hepatocyte nuclear factor 4A (n = 4), glucokinase (n = 8), or hepatocyte nuclear factor 1A (n = 10). Of these 22 subjects, 13 had mutations known to be pathogenic and 9 (41%) had novel mutations, predicted to be pathogenic. Only 1 of the 22 subjects had been given the appropriate MODY diagnosis prior to testing. Compared with MODY-negative subjects, the MODY-positive subjects had lower hemoglobin A1c level and no diabetic ketoacidosis at onset; however, these characteristics are not specific for MODY. In summary, this study found a high frequency of MODY mutations with the majority of subjects clinically misdiagnosed. Clinicians should have a high index of suspicion for MODY in youth with antibody-negative diabetes.
Copyright © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Open access article
Early Online, first published online: 8 JUN 2015